Objectives: (1) To examine whether hyperbaric oxygen (HBO2) will inhibit growth of multidrug-resistant Klebsiella pneumoniae (MDR-K. pneumoniae) and extensively drug-resistant Klebsiella pneumoniae (XDR-K. pneumoniae); (2) To determine whether the effect of tigecycline on XDR-K. pneumoniae will be enhanced by HBO2. Methods: The effects of 1.5 hours of treatment with normoxia (21% O2, 1 atmosphere absolute/ATA) or HBO2 (100% O2, 2 ATA) on bacterial counts of eight isolates of MDR-K. pneumoniae and eight isolates of XDRK. pneumoniae were studied. The effects of five hours of treatment with normoxia (21% O2, 1 ATA), tigecycline (21% O2, 1 ATA), HBO2 (100% O2, 3 ATA) or HBO2 + tigecycline (100% O2, 3 ATA) on proliferation of 10 isolates of XDR-K. pneumoniae were investigated. Results: HBO2 at 100% O2, 2 ATA, 1.5 hours suppressed growth of MDR-K. pneumoniae but had no effect on XDR-K. pneumoniae. HBO2 at 100% O2, 3 ATA, five hours enhanced the effects of tigecycline on XDR-K. pneumoniae. Conclusion: HBO2 in combination with or without tigecycline can be used to eliminate K. pneumoniae in vitro, and such treatment may be beneficial for patients with infections caused by K. pneumoniae.